Pain is the most common reason for physician consultation, and can be caused by a variety of medical conditions and procedures. Both chronic and acute pain can lead to a significant reduction in the quality of life, with many individuals facing long term disablement and handicaps.
Opiates have been the subject of intense research since the isolation of morphine in 1805, and thousands of compounds having opiate or opiate-like activity have been identified. Many opioid receptor-interactive compounds including those used for producing analgesia (e.g., morphine) and those used for treating drug addiction (e.g., naltrexone and cyclazocine) have been employed in human therapy. The actions of endogenous opioids and opiates are mediated by three receptor types (μ, δ, and κ receptors), which are coupled to different intracellular effector systems. [Berrocoso E. et. al., Current Pharmaceutical Design, 15(14) 2009, 1612-22]. As such, agents that can modulate the actions of one or more of the opioid receptor types with selectivity and sensitivity are important to treat the various diseases and disorders regulated by the opioid system. Compounds that bind to opioid receptors are likely to be useful in the treatment of diseases and conditions modulated by opiate receptors.
Traditional opioid analgesics exert their pharmacological activity once they have passed into the central nervous system (CNS). But this can lead to undesirable CNS-mediated side effects, such as respiratory depression, increased drug tolerance, increased drug dependence, constipation and unwanted euphoria. There remains a continuing need for new drugs that can be used to treat or prevent pain, and that reduce or avoid one or more side effects associated with traditional opioid therapy.
While certain treatments for pain do exist, many commonly used analgesics suffer from significant drawbacks including inefficacy, tolerance, and chemical dependence. There is therefore a need for new compounds and methods of treatment for pain that may be used alone or in conjunction with existing therapeutic modalities.